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Introduction: Poor adherence to prescribed treatments is widespread in clinical practice and this can lead to potentially life-threatening events. This problem is apparently very common for osteoporosis treatment but the causes of discontinuation and low compliance are complex and poorly defined. Methods: Global adherence to osteoporosis treatment was specifically addressed in a nation-wide survey carried out in 9851 postmenopausal women referred to 141 Italian centres for osteoporosis management for a follow-up assessment, at least one year after having been prescribed a treatment with one of the following drugs: calcium [+ or -] vitamin D supplements alone (CaVitD), hormone replacement therapy (HRT), raloxifene 60 mg (RLX), intramuscular clodronate 100 mg/7-14 days (CLOD), risedronate 5 mg/day (RIS) and alendronate 10mg/daily (ALN10) or 70 mg once weekly (ALN OW). Results: Overall 19.1% of the patients discontinued the prescribed drug before attending the bone mass reevaluations, more than half of them within the first 6 months. The discontinuation rate was significantly different between the treatments. The medications most frequently interrupted within one year were CLOD (28.7%; p Keywords Adherence * Compliance * Osteoporosis * Persistence * Treatment

Byline: M. Pedrazzoni (1), G. Girasole (2), F. Bertoldo (3), G. Bianchi (2), C. Cepollaro (4), A. Del Puente (5), S. Giannini (6), S. Gonnelli (4), D. Maggio (7), C. Marcocci (8), S. Minisola (9), E. Palummeri (10), M. Rossini (11), L. Sartori (6), L. Sinigaglia (12) Keywords: Bone densitometry; Diagnosis; DXA; Osteoporosis; Reference values Abstract: Osteoporosis is currently defined on the basis of the T-score by dual-energy X-ray absorptiometry (DXA). Despite its limitations, this definition is applied worldwide. However, the normal values provided by manufacturers may not be fully representative of specific local populations. So far, there are no normative data in the Italian population using Hologic densitometers. The Densitometric Italian Normative Study (DINS) is an ongoing multi-center study that aims to establish reference values for bone densitometry with dual-energy X-ray absorptiometry (DXA) in the male and female Italian population. In this paper we report the results of the lumbar vertebrae (L2--L4) and proximal femur in 1,622 women aged 20--79 years. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry (DXA) on Hologic bone densitometers (Hologic, Waltham, Mass.). Most of the subjects were examined with a QDR 4500. The BMD of the lumbar vertebrae was virtually constant between 20 and 49 years (test for trend: P=0.66) the BMD values between 20--45 in premenopausal women (mean 1.036 SD 0.109 g/cm.sup.2) were thus defined as the peak bone mass values, significantly lower compared to the Hologic reference curve (mean 1.079, SD 0.11 g/cm.sup.2). The mean BMD values of the femoral neck were virtually identical to those of the NHANES study in the first 3 decades after the age of 50 the BMD values were slightly greater than those of the NHANES subject. The subject classification according to the WHO criteria was similar using the DINS and NHANES reference values for the femur for the spine, the Hologic reference values classified a larger proportion of women as osteoporotic (21 vs. 16%) or osteopenic (42 vs. 38%) compared to DINS. Author Affiliation: (1) Dipartimento di Medicina Interna e Scienze Biomediche, Universita di Parma, Via Gramsci 14, 43100 , Parma, Italy (2) Divisione di Reumatologia, Dipartimento Apparato Locomotore, ASL 3 Genovese, Genova, Italy (3) Dipartimento di Scienze Biomediche e Chirurgiche, Universita di Verona, Verona, Italy (4) Dipartimento di Medicina Interna, Scienze Endocrino-Metaboliche e Biochimica, Universita di Siena, Siena, Italy (5) Reumatologia, Universita 'Federico II', Napoli, Italy (6) Dipartimento di Scienze Mediche e Chirurgiche, Universita di Padova, Padova, Italy (7) Gerontologia e Geriatria, Universita di Perugia, Perugia, Italy (8) Dipartimento di Endocrinologia e Metabolismo, Universita di Pisa, Pisa, Italy (9) Dipartimento di Scienze Cliniche, Universita di Roma 'La Sapienza', Roma, Italy (10) Dipartimento Interaziendale di Geriatria, ASL 3--Ospedali Galliera, Genova, Italy (11) Centro Osteoporosi, Universita-ASL di Verona, Verona, Italy (12) Servizio Malattie Osteometaboliche, Dipartimento di Reumatologia, Istituto G. Pini, Milano, Italy Article History: Received Date: 14/02/2003 Accepted Date: 05/09/2003 Online Date: 03/10/2003

Byline: M. Varenna (1), L. Binelli (1), F. Zucchi (1), V. Rossi (1), L. Sinigaglia (1) Keywords: Epidemiology; Ethnic group; Fractures; Italy; Migrant study; Osteoporosis Abstract: The purpose of this study was to assess whether a migrant population from southern regions of Italy showed differences in osteoporosis (OP) and fracture prevalence in comparison to a population born and living in Milan, a city in northern Italy. The study group consisted of 1764 postmenopausal women born in southern Italy who migrated after age 20 to Milan, where they had lived for at least 15 years. This group was compared with a sample of 4018 postmenopausal women born, raised and living in Milan. Bone mineral density (BMD) was measured at lumbar spine by dual-energy X-ray absorptiometry. Univariate analysis showed a significantly higher BMI, a greater parity, a lower postmenopausal estrogen (HRT) usage and a lower calcium intake in the Southern group (SG). Densitometric values showed a mean lumbar BMD significantly lower in SG (P&lt 0.001), resulting in a greater prevalence of OP (30.5% versus 24.9% P&lt 0.001). Consistent with this result, the number of women reporting low energy fractures after menopause was higher in SG (4.8% versus 3.6% P=0.01). Multiple logistic regression analyses showed that OP was predicted by well-recognized variables, such as age, age at menopause, BMI, HRT, calcium intake together to belonging to SG, which independently increased the risk for OP by 42%. Age, age at menopause, BMI and belonging to SG significantly influenced the fracture risk, but the last variable was no longer associated with an increased fracture risk when BMD was entered in the model. Despite the results of previous epidemiological studies and protective anthropometric measures, a higher OP and fracture prevalence was found in the migrant group from southern Italy to Milan in comparison with the native sample. These differences are not solely explained by lifestyle variables. Our data suggest that changing environmental exposures can influence bone mass and fracture risk. Author Affiliation: (1) Department of Rheumatology. Istituto Ortopedico 'Gaetano Pini', Via G. Pini 9, I-20122, Milan, Italy Article History: Received Date: 13/11/2002 Accepted Date: 28/03/2003 Online Date: 10/07/2003

Byline: M. Varenna (1), L. Binelli (1), F. Zucchi (1), D. Ghiringhelli (1), L. Sinigaglia (1) Keywords: Key words:Calcium intake -- Cholesterol -- Osteoporosis -- Risk factors -- Wrist fracture Abstract: The purpose of this study was to assess whether dietary changes aimed at reducing serum cholesterol can increase the risk of osteoporosis (OP) and fracture. The study group consisted of 311 postmenopausal women with high serum cholesterol levels and following a diet low in dairy products (calcium intake estimated at less than 300 mg/day) for 27.3 +- 29.1 months. This sample was compared with a case--control group of 622 healthy postmenopausal women paired for age and age at menopause and with a calcium intake estimated at more than 1 g/day. Bone mineral density was measured at the lumbar spine by dual-energy X-ray absorptiometry. Prevalence of OP was significantly higher in women with a low dairy calcium intake (42.1% vs 22.3% p&lt 0.0001), as was the number of Colles' fractures occurring after menopause (4.5% vs 1.6% p = 0.008). Multiple logistic regression analyses demonstrated that a diet low in dairy calcium was a risk factor for OP (OR = 2.52, 95% CI 1.84--3.45) and Colles' fracture (OR = 2.72, 95% CI 1.18--6.26). In the low dairy calcium group, diet duration significantly influenced the risk of OP (OR = 1.13, 95% CI 1.01--1.25 for 1 year of diet). No differences in further risk factors for coronary heart disease were found between the groups, but the proportion of women physically active was lower in the women with high serum cholesterol levels. A diet that severely limits calcium intake from dairy products in an attempt to correct raised serum cholesterol levels is a risk factor for postmenopausal OP and Colles' fracture. Dietary intervention methods to lower serum cholesterol in postmenopausal women should maintain an adequate calcium intake by providing calcium from low-fat dairy products or calcium supplements. Author Affiliation: (1) Department of Rheumatology, Istituto Ortopedico 'Gaetano Pini', Milan, Italy, IT Article note: Received: 16 May 2000 / Accepted: 18 November 2000

Byline: M. Varenna (1), L. Binelli (1), F. Zucchi (1), D. Ghiringhelli (1), M. Gallazzi (2), L. Sinigaglia (1) Keywords: Key words:Formal Education -- Osteoporosis -- Risk factors Abstract: To evaluate whether the prevalence of osteoporosis and related risk factors might be influenced by the level of education, as has been demonstrated for many other chronic diseases, 6160 postmenopausal women at their first densitometric referral were interviewed about reproductive variables, past and current use of estrogens, prevalence of chronic diseases, and lifestyle factors such as calcium intake, physical activity, smoking and overweight. This sample was stratified by years of formal education. Densitometric evaluation was performed by dual-energy X-ray absorptiometry. Age at menarche, past exposure to oral contraceptives, use of hormone replacement therapy, prevalence of chronic diseases, physical activity, overweight and smoking showed significant trends according to the years of education. The prevalence of osteoporosis showed an inverse relationship with level of education, ranging from 18.3% for the most educated to 27.8% for the least educated women. Multiple logistic regression analysis demonstrated a predictive role toward osteoporosis by age, age at menarche and menopause, hormone replacement therapy, calcium intake, physical activity and body mass index. Using the lowest educational level as reference category, increases in educational status were associated with a significantly reduced risk for osteoporosis (OR = 0.76, 95% CI 0.65--0.90 for 6--8 years of schooling OR = 0.68, 95% CI 0.57--0.82 for 9 years or more). This study shows differences in the prevalence of osteoporosis among educational classes and the protective role played by increases in formal education. If these results are confirmed in other population studies, public health intervention programs will have to consider the socioeconomic and cultural background of the population strata that run a greater risk of osteoporosis. Author Affiliation: (1) Chair of Rheumatology, University of Milan and, IT (2) Department of Radiology, Istituto Ortopedico 'Gaetano Pini', Milan, Italy, IT Article note: Received: 7 March 1998 / Accepted: 9 July 1998

To assess, in a setting close to real life, the efficacy and safety of weekly subcutaneous tocilizumab (TCZ-SC) 162 mg, alone or with a conventional synthetic DMARD (csDMARD), in moderate-to-severe RA patients with inadequate response to DMARDs or anti-TNFα drugs. This national, multicenter, open-label, phase IIIb trial is part of an umbrella study (TOZURA). Patients were treated for 52 weeks followed by 8 weeks drug-free to evaluate immunogenicity. The primary end point was the Clinical Disease Activity Index (CDAI) change from baseline at weeks 2 and 24. Other efficacy parameters, including sleep quality, and the safety and immunogenicity were also assessed up to week 52. Of 288 patients enrolled in 43 Italian centers, 78.8% received TCZ-SC (86.8% females; mean age 54.7 ± 12.1 years; mean disease duration 7.8 ± 7.5 years; DMARD-IRs 94.7%). Of these, 78.0% completed the 52-week period and 52.0% received concomitant methotrexate. TCZ-SC yielded a significant reduction in median CDAI from baseline already at week 2, which progressed up to week 24 and remained stable thereafter (P < 0.0001 at each time point). A significant, rapid, and sustained improvement of the other efficacy variables was also observed. Patients were deemed as ready for home administration after a median of 2.0 (range 1-8) administrations, with a rate (since the last visit) of 80.6% and 95.5% at weeks 2 and 52, respectively. TCZ-SC displayed low immunogenicity and no unexpected toxicities. TCZ-SC, alone or with a csDMARD, yielded rapid and sustained efficacy in DMARD/anti-TNFα-IR RA patients, with acceptable toxicity. Home administration seems feasible.

To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics' registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.

The purpose of the study was to estimate the clinical profile of naïve biological patients with rheumatoid arthritis (RA) starting adalimumab through 3-year calendar periods and their clinical outcomes such as drug survival and global clinical disease control (GCDC). RA patients starting adalimumab as first biological drug between 2003 and 2012 were subdivided in 3-year calendar periods. Survival on therapy was estimated using the Kaplan-Meier analysis. One and 2-year clinical response was assessed by calculating percentage of patients attaining GCDC (28-joint Disease Activity Score (DAS28) ≤ 2.6 + Health Assessment Questionnaire (HAQ) ≤ 0.5), low disease activity (DAS28 ≤ 3.2), remission (DAS28 ≤ 2.6) and good European League Against Rheumatism (EULAR) response. Multivariate regression models were used to assess baseline predictors of drug discontinuation or achievement of clinical remission. We recruited 1695 RA patients. Overall drug persistence at 3 years was 40.6 %, while the global rate of nonswitching patients was 54.7 %. Compared to 2003-2005, initiators in more recent years had a significantly lower 3-year crude drug retention rate (log rank, p < 0.0001) and a significantly higher rate of switching to alternative biologics (log rank, p < 0.0001). No difference in adverse events or effectiveness rate among the calendar periods was found. A substantial proportion of patients (up to 27 %) achieved GCDC at 2 years, regardless of the calendar period. In real-life setting, RA patients starting adalimumab in more recent years had a higher rate of drug discontinuation not related to ineffectiveness or side effects but to switching, probably due to a wider availability of biologics. A meaningful proportion of patients attained GCDC without any difference across calendar periods.

Corticosteroids remain a key component in the management of many disorders. Bone loss resulting from long-term administration of these drugs is common and osteoporosis induced by corticosteroids is the most frequent cause of secondary osteoporosis in nearly 50% of individuals on chronic corticosteroid therapy suffering from an osteoporotic fracture at some point. This article reviews the epidemiology and pathogenesis of glucocorticoid-induced osteoporosis.

Three new cases of transient osteoporosis of the hip are reported. Diagnosis was achieved by plain radiographs, bone scintiscan, magnetic resonance imaging and X-ray absorptiometry of proximal femurs. The densitometry showed at the Ward's triangle a mean reduction of bone mineral density in the affected side of 36%. All subjects were treated with i.v. clodronate for ten consecutive days with a complete recovery of femoral density within 4 months. X-ray absorptiometry allows a quantification of the demineralization process and can be useful in the long term evaluation of this entity.

The plasma and synovial fluid concentrations of synthetic salmon calcitonin in 10 patients with knee joint effusions have been compared after a single i.v. dose of 200 I.U. calcitonin. Plasma and synovial fluid concentrations of calcitonin were measured using a specific RIA before and 30 and 60 min after administration. Calcitonin was not detectable at zero time in plasma or in synovial fluid. Plasma calcitonin concentrations 60 min after administration were significantly lower than at 30 min, while the synovial fluid concentration remained relatively constant. The results show that synthetic salmon calcitonin penetrates into the articular cavity after a single i.v. dose of 200 I.U. and that a steady concentration persists there over 60 min.